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Principal Investigator: John C Alverdy
Organization: COVIRA SURGICAL
Fiscal Year: 2024
Award: $400,000
Funding agency: National Cancer Institute
PROJECT SUMMARY
Covira Surgical, Inc. is developing a first-in-class agent for preventing chemotherapy-related
gastrointestinal (GI) toxicities and lethal infections. Chemotherapy renders patients more susceptible to
infection - many if most of which originate from the gastrointestinal track flora. Chemotherapy causes a major
disruption in the gastrointestinal tract structure (i.e., mucosal ulceration, loss of tight junction permeability,
submucosal edema, inflammatory cell infiltrations, etc.) and microbiome (i.e., dysbiosis). As a result,
chemotherapy induced GI tract toxicity can lead to treatment disruptions, potential cancer progression, additional
hospitalizations, and increased mortality. Compared to the general population, cancer patients have a mortality
rate of fatal infections almost three times higher. Given these facts, infection is considered one of the most
serious chemotherapy-related toxicities and many, if not most patients receive antibiotics during the course of
their chemotherapy which can lead to further acquisition of antibiotics resistant strains of bacteria. Therefore,
there is an urgent need for novel therapies to help reduce chemotherapy-related GI toxicities and infections that
do not involve the addition of broader and more powerful antibiotics.
Covira Surgical, Inc. intends to address this urgent need by developing a first-in-class agent capable of
preserving the beneficial effects of the gut microbiome while suppressing its harmful effects. The gut microbiome
plays a key role in modulating chemotherapy-related toxicity and efficacy, drug metabolism, and tumor
microenvironment. Our agent – CS-0003 – is a novel, orally administered, non-antibiotic phosphate-rich
mucoadhesive polyethylene glycol. CS-0003 can promote the retention and growth of the native microbiome
while suppressing the proliferation and dissemination of lethal pathogens from the gut. CS-0003 provides
microbes with a readily available source of phosphate while physically shielding bacteria away from the
endothelial surface, thus behaving as a surrogate mucin that cannot be absorbed. This approach allows the gut
microbiome to positively influence the immune system and GI tract. Our animal studies to date have
demonstrated that CS-0003 is distributed along the entire GI tract and is safe and well-tolerated. Successful
completion of this Phase I project will demonstrate that CS-0003 is safe and efficacious in ameliorating
chemotherapy-induced toxicity and infection in mice treated with two common chemotherapeutic agents.
Terms: <16S gene sequencing><16S rRNA amplicon sequencing><16S rRNA gene amplicon sequencing><16S rRNA gene sequencing><16S rRNA genomic profiling><16S rRNA sequencing><16S ribosomal RNA gene sequencing><16S ribosomal RNA sequencing><16S sequencing><Address><Alimentary Canal><American><Anemia><Animals><Antibiotic Agents><Antibiotic Drugs><Antibiotic Resistance><Antibiotics><Area><Attention><Bacteremia><Bacteria><Bacterial Infections><Bacterial Translocation><Blood><Blood Reticuloendothelial System><Campto><Cancer Patient><Cancer Treatment><Cecum><Cell Body><Cell Components><Cell Structure><Cells><Cellular Structures><Cessation of life><Ciprofloxacin><Colon><Colorectal Cancer><Consumption><Data><Death><Death Rate><Development><Diarrhea><Diet><Digestive Tract><Disease Progression><Dropsy><Edema><Endothelium><Epithelium><Exposure to><Fatality rate><Fatigue><Future><GI Tract><GI microbiome><GI microbiota><Gastrointestinal Tract><Gastrointestinal microbiota><Gastrointestinal tract structure><General Population><General Public><Generalized Growth><Goals><Growth><Gut Epithelium><Histology><Hospital Admission><Hospitalization><Human><Hydrogen Oxide><Hydrops><Immune system><Infection><Infiltration><Inflammatory><Injury><Lack of Energy><Legal patent><Life><Liver><Macrogols><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Marketing><Measures><Methotrexate><Methotrexate Methylaminopterin><Methotrexatum><Metotrexato><Mice><Mice Mammals><Microbe><Miscellaneous Antibiotic><Modeling><Modern Man><Mucins><Mucosa><Mucosal Tissue><Mucous Membrane><Mucus Glycoprotein><Murine><Mus><Nephrotoxic><Occluding Junctions><Operative Procedures><Operative Surgical Procedures><Oral><Oral Administration><Oral Drug Administration><Patents><Pathology><Patients><Permeability><Phase><Phosphates><Phosphorylation><Play><Polyethylene Glycols><Polyethylene Oxide><Polyethyleneoxide><Polyoxyethylenes><Predisposition><Progenitor Cells><Proliferating><Protein Phosphorylation><QOL><Quality of life><Resistance to antibiotics><Resistant to antibiotics><Rodent><Rodentia><Rodents Mammals><Sampling><Sepsis><Source><Spleen><Spleen Reticuloendothelial System><Submucosa><Surface><Surgical><Surgical Interventions><Surgical Procedure><Susceptibility><Therapeutic><Tight Junctions><Tissue Growth><Toxic effect><Toxicities><Treatment-related toxicity><Ulcer><Ulceration><Villus><Water><Weight><Zonula Occludens><absorption><alimentary tract><anti-cancer therapy><antibiotic drug resistance><antibiotic resistant><bacteraemia><bacteria infection><bacterial disease><bacterial sepsis><blood infection><bloodstream infection><camptosar><cancer microenvironment><cancer progression><cancer therapy><cancer-directed therapy><chemotherapeutic agent><chemotherapy><copolymer><death risk><determine efficacy><developmental><diets><digestive canal><digestive tract microbiome><drinking><drinking water><drug metabolism><dysbacteriosis><dysbiosis><dysbiotic><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><efficacy testing><enteric microbial community><enteric microbiome><enteric microbiota><evaluate efficacy><examine efficacy><gastrointestinal><gastrointestinal epithelium><gastrointestinal microbial flora><gastrointestinal microbiome><gut commensal><gut community><gut flora><gut microbe community><gut microbial community><gut microbial composition><gut microbial consortia><gut microbiome><gut microbiota><gut microbiotic><gut microflora><gut-associated microbiome><hepatic body system><hepatic organ system><high-fat/low-fiber diet><ileum><improved><improved outcome><injuries><injury to the intestines><inorganic phosphate><intestinal biome><intestinal flora><intestinal injury><intestinal microbiome><intestinal microbiota><intestinal microflora><intestinal tract microflora><intraoral drug delivery><irinotecan><jejunum><kidney toxicity><microbial imbalance><microbiome><microbiome sequencing><mortality><mortality rate><mortality ratio><mortality risk><neoplasm progression><neoplastic progression><nephrotoxicity><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><ontogeny><pathogen><preservation><prevent><preventing><progenitor cell function><progenitor function><protective effect><resistance strain><resistant strain><stem and progenitor cell function><stem and progenitor function><stem cell function><stem cells><surgery><therapeutic toxicity><therapy associated toxicity><therapy related toxicity><therapy toxicity><treatment toxicity><treatment-associated toxicity><tumor microenvironment><tumor progression><weights><western diet><western-style diet><western-type diet>